- Email: [email protected]
Reduced Blood Pressure and Risk of Future Cardiovascular Disease from a Structured Care Algorithm in Primary Care Patients with Persistent Hypertension: A Multicentre Randomised Controlled Trial
S22
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
by a reduction in LV hypertrophy, and persistent PHT in a subset which may suggest irreversible PA remodelling. http://dx.doi.org/10.1016/j.hlc.2012.05.058 49 Pulmonary Vascular Capacitance Measured Using Pressurewire: A Novel Index of Pulmonary Haemodynamics Moneghetti ∗ ,
50 Redox Regulation of Na+ –K+ Pump in Vascular Smooth Muscle Cells: Implications for Vascular Tone in Heath and Disease K. Karimi Galougahi 1,2,∗ , C. Liu 1 , A. Nunez 1 , A. Garcia 1 , N. Fry 1 , H. Rasmussen 1,2 , G. Figtree 1,2 1 North Shore Heart Research Group, Kolling Institute, Australia
S. Palmer, S. Murch, A. LaGerche, D. K. Prior, A. MacIsaac, A. Burns
2 Cardiology
St Vincent’s Hospital, Australia
Na+ –K+ pump establishes electrochemical gradient across membrane in vascular smooth muscle cells (VSMCs) and is a determinant of vascular tone through effects on intracellular Ca2+ homeostatsis, but its regulation in vessels is poorly understood. We examined if glutathionylation of Na+ –K+ pump’s 1 subunit, a reversible oxidative modification shown to inhibit the pump in cardiac myocytes, occurs in VSMCs and is of physiological significance. Glutathionylation of 1 subunit was detected in rabbit VSMCs at baseline and was increased by the chemical oxidant S-nitrosoglutathion, causing a reduction in pump activity. Angiotensin II (Ang II), known to activate NADPH oxidase, increased 1 glutathionylation in VSMCs, rabbit aorta and human arteries ex vivo; and reduced pump activity in VSMCs and rabbit aorta as measured by K+ -induced relaxation of vessels pre-incubated in K+ -free solutions. Incubation of cells or vessels with gp91ds-tat, a peptide inhibitor of NADPH oxidase, abolished the Ang II effects on glutathionylation and pump activity. Angiotensin converting enzyme inhibition in vivo reduced 1 glutathionylaytion and enhanced pump activity, measured as K+ -induced relaxation, in rabbit aorta. FXYD proteins associate with the pump and play a role in regulation by facilitating “deglutathionylation” in cardiac myocytes. Recombinant FXYD3 competitively displaced native FXYD1 in VSMCs and rabbit aorta, and abolished the Ang II-induced increase in 1 glutathionylation and the reduction in pump activity. We identify a mechanism for redox regulation of Na+ –K+ pump in VSMCs with pathophysiological significance in conditions like hypertension that are characterised by oxidative stress and abnormal regulation of vascular tone.
Purpose: Pulmonary hypertension (PH) is associated with a poor prognosis regardless of aetiology. Reduced pulmonary vascular capacitance, in addition to increased resistance, may be an important determinant of pulmonary afterload and thus increasing pulmonary pressure. Methods: Subjects referred for diagnostic right heart catheterisation with suspected PH underwent assessment of pulmonary haemodynamics pre- and post-IV adenosine using a pressure and temperature-sensing guidewire (PressureWire) positioned in a second order branch pulmonary artery (PA) providing high fidelity pressure measurement and thermodilution derived mean transit time (Tmn). Capacitance index (CI, mL/mmHg) was defined as 1000/(heart rate × PA pulse pressure × Tmn). Diastolic dysfunction (DD) was defined as LVEDP greater than 18 mmHg and PH as mean PA pressure greater than 25 mmHg. Results: Thirty-one consecutive patients were analysed: 10 with pulmonary arterial hypertension (PAH, either primary or secondary to scleroderma), six had DD with PH, seven had both scleroderma and DD, four had mitral valve disease and four were normal. Adenosine infusion resulted in decreased Tmn (0.47 ± 0.05 vs 0.33 ± 0.03, p < 0.001) and increased CI (1.79 ± 0.28 vs 2.33 ± 0.3, p < 0.005), but no change in heart rate nor mean PA pressure. Higher PA pressure was associated with lower CI, both pre adenosine (r = −0.62, p < 0.003) and post adenosine (r = −0.54, p < 0.003). Conclusion: Capacitance index is reduced with increasing severity of PH and to a greater extent in patients with PAH than those with DD. This novel index may have utility in early diagnosis and tracking subtle changes in haemodynamics in patients with PH. http://dx.doi.org/10.1016/j.hlc.2012.05.059
Department, Royal North Shore Hospital,
Australia
http://dx.doi.org/10.1016/j.hlc.2012.05.060 51 Reduced Blood Pressure and Risk of Future Cardiovascular Disease from a Structured Care Algorithm in Primary Care Patients with Persistent Hypertension: A Multicentre Randomised Controlled Trial M. Carrington 1,∗ , G. Kurstjens 2 , S. Stewart 1 1 Baker
Jennings 1 , C.
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Background: To determine the impact of reduced blood pressure (BP) on CVD risk in hypertensive primary care
CSANZ 2012 Abstracts
http://dx.doi.org/10.1016/j.hlc.2012.05.061
ence in the concentrations of ET-1 between AF patients and REF subjects. In RMS patients and REF subjects there were no differences in concentrations of ET-1 between the FV, RA and LA. In contrast, there was a decrease in concentrations of ET-1 in the RA and LA of AF patients compared to FV (p < 0.03 and p < 0.06, respectively). Endothelin-1 Levels 3
* 2
1
0 FV RA LA
Rheumatic Mitral Stenosis is Associated with Elevated Endothelin-1 Levels Willoughby 1,∗ ,
Scultz 1 ,
Kumar 2 ,
Priya 3 ,
S. C. S. S. S. Nair 3 , A. Srivastava 3 , G. Joseph 2 , O. George 2 , P. Pati 2 , D. Chase 2 , S. Chandy 2 , B. John 2 , P. Sanders 1 1 Centre
for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia 2 Department of Cardiology, Christian Medical College, Vellore, India 3 Department of Haematology, Christian Medical College, Vellore, India Background: It is well established that rheumatic mitral stenosis (RMS) and atrial fibrillation (AF) are associated with an increased risk of thromboembolic events. Endothelin-1 (ET-1) is a potent vasoconstrictor and modulator of endothelial function, and is known to play a role in thrombus formation. We therefore sought to compare ET-1 levels between patients with RMS and atrial fibrillation. Methods: We measured plasma levels of ET-1 in blood samples from the femoral vein (FV), right atria (RA) and left atria (LA) obtained from 19 patients with RMS, 12 patients with AF and 10 subjects with supraventricular tachycardia (reference subjects [REF]). Plasma ET-1 levels were measured by ELISA. Results: The FV concentrations of ET-1 were significantly higher in RMS patients then in AF patients or REF subjects (figure). However, there was no significant differ-
FV RA LA
FV RA LA
Conclusion: Patients with RMS stenosis have significantly higher ET-1 levels than patients with AF. These data suggest that ET-1 plays a differential role in the pathophysiology of thrombus formation in RMS and AF. http://dx.doi.org/10.1016/j.hlc.2012.05.062 53 Sorting the Wheat from the Chaff: Initial Blood Pressure Control in the VIPER-BP Study Cohort of Primary Care Patients with Previously Uncontrolled Hypertension Carrington 1 , C. S. Stewart 1,∗ , M. 2 Kurstjens , G. Jennings 1 1 Baker
52
REF subjects Rheumatic mitral stenosis Atrial fibrillation
pg/ml
patients randomised to usual care (UC) or an algorithm to optimise BP control in the Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) Study. Methods: Prospective, multi-centre RCT involving 119 primary care clinics. Based on 26 week follow-up data we used (a) change in risk profile and (b) age, initial systolic and diastolic BP and change in BPs, to calculate changes in absolute five year cardiovascular risk score (ACVRS) and relative risk (RR) of a future coronary artery disease (CAD) or stroke event. Results: 1562 patients (59 ± 12 years, 62% men, 67% prior hypertension and BP 150 ± 17/88 ± 11 mmHg) remaining above their individualised BP target were randomised (1:2 ratio) to UC (n = 524) or the VIPER-BP intervention (n = 1038). Consistent with significantly greater falls in BP in favour of the VIPER-BP intervention, mean falls in ACVRS (from baseline) were greatest in VIPER-BP versus UC patients (−3.7 ± 4.5% vs. −2.6 ± 4.5%, adjusted mean difference −1.13, 95% CI −1.63 to −0.64%, p < 0.001). Similarly, the adjusted risk of CAD (RR 0.75 ± 0.36 vs. 0.81 ± 0.39; p < 0.001) and stroke (RR 0.69 ± 0.49 vs. 0.80 ± 0.52; p < 0.001) was attenuated most in the VIPER-BP group. Conclusions: A structured care algorithm to optimise primary care management of hypertension not only results in lowered BP, but reduces ACVRS and RR of future CVD.
S23
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Purpose: We determined the early impact of standardised profiling and anti-hypertensive treatment on early blood pressure (BP) control in hypertensive patients. Methods: The Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) Study, was a prospective, multi-centre randomised controlled trial of a more intensive approach to BP management. We enrolled 2337 patients from 119 primary care clinics with elevated BP with 2185 commencing a standardised “run-in” phase of automated risk profiling and anti-hypertensive therapy (valsartan 80 mg/day for 14–28 days). Results: Overall, 1978 patients (60% men, aged 59 ± 12 years and 61% prior hypertension) completed “run-in”. Initial BP targets were ≤140/90 (41%), ≤130/80 (44%) and ≤125/75 mmHg (15%). Subsequently, 34%, 14% and 7% of patients, respectively, achieved their individual BP target. On an adjusted basis, these patients were more likely to be female (OR 1.43, 95% CI 1.13–1.82; p = 0.003). Alternatively, those with prior hypertension (OR 0.27, 95% CI 0.21–0.35), higher initial systolic (OR 0.96, 95% CI 0.95–0.98 per mmHg) and diastolic (OR 0.97, 95% CI 0.96–0.98 per mmHg) BP and an increasingly stricter BP target (reference group ≤140/90 mmHg, OR 0.24, 95% CI 0.08–0.204 and OR 0.13, 95% CI 0.19–0.31 for the two lower BP targets) were less likely to achieve early BP control. Conclusions: An initial period of profiling and simplified treatment achieved subsequent BP control in almost one in five patients being treated for hypertension. These
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
by a reduction in LV hypertrophy, and persistent PHT in a subset which may suggest irreversible PA remodelling. http://dx.doi.org/10.1016/j.hlc.2012.05.058 49 Pulmonary Vascular Capacitance Measured Using Pressurewire: A Novel Index of Pulmonary Haemodynamics Moneghetti ∗ ,
50 Redox Regulation of Na+ –K+ Pump in Vascular Smooth Muscle Cells: Implications for Vascular Tone in Heath and Disease K. Karimi Galougahi 1,2,∗ , C. Liu 1 , A. Nunez 1 , A. Garcia 1 , N. Fry 1 , H. Rasmussen 1,2 , G. Figtree 1,2 1 North Shore Heart Research Group, Kolling Institute, Australia
S. Palmer, S. Murch, A. LaGerche, D. K. Prior, A. MacIsaac, A. Burns
2 Cardiology
St Vincent’s Hospital, Australia
Na+ –K+ pump establishes electrochemical gradient across membrane in vascular smooth muscle cells (VSMCs) and is a determinant of vascular tone through effects on intracellular Ca2+ homeostatsis, but its regulation in vessels is poorly understood. We examined if glutathionylation of Na+ –K+ pump’s 1 subunit, a reversible oxidative modification shown to inhibit the pump in cardiac myocytes, occurs in VSMCs and is of physiological significance. Glutathionylation of 1 subunit was detected in rabbit VSMCs at baseline and was increased by the chemical oxidant S-nitrosoglutathion, causing a reduction in pump activity. Angiotensin II (Ang II), known to activate NADPH oxidase, increased 1 glutathionylation in VSMCs, rabbit aorta and human arteries ex vivo; and reduced pump activity in VSMCs and rabbit aorta as measured by K+ -induced relaxation of vessels pre-incubated in K+ -free solutions. Incubation of cells or vessels with gp91ds-tat, a peptide inhibitor of NADPH oxidase, abolished the Ang II effects on glutathionylation and pump activity. Angiotensin converting enzyme inhibition in vivo reduced 1 glutathionylaytion and enhanced pump activity, measured as K+ -induced relaxation, in rabbit aorta. FXYD proteins associate with the pump and play a role in regulation by facilitating “deglutathionylation” in cardiac myocytes. Recombinant FXYD3 competitively displaced native FXYD1 in VSMCs and rabbit aorta, and abolished the Ang II-induced increase in 1 glutathionylation and the reduction in pump activity. We identify a mechanism for redox regulation of Na+ –K+ pump in VSMCs with pathophysiological significance in conditions like hypertension that are characterised by oxidative stress and abnormal regulation of vascular tone.
Purpose: Pulmonary hypertension (PH) is associated with a poor prognosis regardless of aetiology. Reduced pulmonary vascular capacitance, in addition to increased resistance, may be an important determinant of pulmonary afterload and thus increasing pulmonary pressure. Methods: Subjects referred for diagnostic right heart catheterisation with suspected PH underwent assessment of pulmonary haemodynamics pre- and post-IV adenosine using a pressure and temperature-sensing guidewire (PressureWire) positioned in a second order branch pulmonary artery (PA) providing high fidelity pressure measurement and thermodilution derived mean transit time (Tmn). Capacitance index (CI, mL/mmHg) was defined as 1000/(heart rate × PA pulse pressure × Tmn). Diastolic dysfunction (DD) was defined as LVEDP greater than 18 mmHg and PH as mean PA pressure greater than 25 mmHg. Results: Thirty-one consecutive patients were analysed: 10 with pulmonary arterial hypertension (PAH, either primary or secondary to scleroderma), six had DD with PH, seven had both scleroderma and DD, four had mitral valve disease and four were normal. Adenosine infusion resulted in decreased Tmn (0.47 ± 0.05 vs 0.33 ± 0.03, p < 0.001) and increased CI (1.79 ± 0.28 vs 2.33 ± 0.3, p < 0.005), but no change in heart rate nor mean PA pressure. Higher PA pressure was associated with lower CI, both pre adenosine (r = −0.62, p < 0.003) and post adenosine (r = −0.54, p < 0.003). Conclusion: Capacitance index is reduced with increasing severity of PH and to a greater extent in patients with PAH than those with DD. This novel index may have utility in early diagnosis and tracking subtle changes in haemodynamics in patients with PH. http://dx.doi.org/10.1016/j.hlc.2012.05.059
Department, Royal North Shore Hospital,
Australia
http://dx.doi.org/10.1016/j.hlc.2012.05.060 51 Reduced Blood Pressure and Risk of Future Cardiovascular Disease from a Structured Care Algorithm in Primary Care Patients with Persistent Hypertension: A Multicentre Randomised Controlled Trial M. Carrington 1,∗ , G. Kurstjens 2 , S. Stewart 1 1 Baker
Jennings 1 , C.
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Background: To determine the impact of reduced blood pressure (BP) on CVD risk in hypertensive primary care
CSANZ 2012 Abstracts
http://dx.doi.org/10.1016/j.hlc.2012.05.061
ence in the concentrations of ET-1 between AF patients and REF subjects. In RMS patients and REF subjects there were no differences in concentrations of ET-1 between the FV, RA and LA. In contrast, there was a decrease in concentrations of ET-1 in the RA and LA of AF patients compared to FV (p < 0.03 and p < 0.06, respectively). Endothelin-1 Levels 3
* 2
1
0 FV RA LA
Rheumatic Mitral Stenosis is Associated with Elevated Endothelin-1 Levels Willoughby 1,∗ ,
Scultz 1 ,
Kumar 2 ,
Priya 3 ,
S. C. S. S. S. Nair 3 , A. Srivastava 3 , G. Joseph 2 , O. George 2 , P. Pati 2 , D. Chase 2 , S. Chandy 2 , B. John 2 , P. Sanders 1 1 Centre
for Heart Rhythm Disorders, University of Adelaide, Adelaide, Australia 2 Department of Cardiology, Christian Medical College, Vellore, India 3 Department of Haematology, Christian Medical College, Vellore, India Background: It is well established that rheumatic mitral stenosis (RMS) and atrial fibrillation (AF) are associated with an increased risk of thromboembolic events. Endothelin-1 (ET-1) is a potent vasoconstrictor and modulator of endothelial function, and is known to play a role in thrombus formation. We therefore sought to compare ET-1 levels between patients with RMS and atrial fibrillation. Methods: We measured plasma levels of ET-1 in blood samples from the femoral vein (FV), right atria (RA) and left atria (LA) obtained from 19 patients with RMS, 12 patients with AF and 10 subjects with supraventricular tachycardia (reference subjects [REF]). Plasma ET-1 levels were measured by ELISA. Results: The FV concentrations of ET-1 were significantly higher in RMS patients then in AF patients or REF subjects (figure). However, there was no significant differ-
FV RA LA
FV RA LA
Conclusion: Patients with RMS stenosis have significantly higher ET-1 levels than patients with AF. These data suggest that ET-1 plays a differential role in the pathophysiology of thrombus formation in RMS and AF. http://dx.doi.org/10.1016/j.hlc.2012.05.062 53 Sorting the Wheat from the Chaff: Initial Blood Pressure Control in the VIPER-BP Study Cohort of Primary Care Patients with Previously Uncontrolled Hypertension Carrington 1 , C. S. Stewart 1,∗ , M. 2 Kurstjens , G. Jennings 1 1 Baker
52
REF subjects Rheumatic mitral stenosis Atrial fibrillation
pg/ml
patients randomised to usual care (UC) or an algorithm to optimise BP control in the Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) Study. Methods: Prospective, multi-centre RCT involving 119 primary care clinics. Based on 26 week follow-up data we used (a) change in risk profile and (b) age, initial systolic and diastolic BP and change in BPs, to calculate changes in absolute five year cardiovascular risk score (ACVRS) and relative risk (RR) of a future coronary artery disease (CAD) or stroke event. Results: 1562 patients (59 ± 12 years, 62% men, 67% prior hypertension and BP 150 ± 17/88 ± 11 mmHg) remaining above their individualised BP target were randomised (1:2 ratio) to UC (n = 524) or the VIPER-BP intervention (n = 1038). Consistent with significantly greater falls in BP in favour of the VIPER-BP intervention, mean falls in ACVRS (from baseline) were greatest in VIPER-BP versus UC patients (−3.7 ± 4.5% vs. −2.6 ± 4.5%, adjusted mean difference −1.13, 95% CI −1.63 to −0.64%, p < 0.001). Similarly, the adjusted risk of CAD (RR 0.75 ± 0.36 vs. 0.81 ± 0.39; p < 0.001) and stroke (RR 0.69 ± 0.49 vs. 0.80 ± 0.52; p < 0.001) was attenuated most in the VIPER-BP group. Conclusions: A structured care algorithm to optimise primary care management of hypertension not only results in lowered BP, but reduces ACVRS and RR of future CVD.
S23
Swemmer 2 , N.
IDI Heart and Diabetes Institute, Australia Pharmaceuticals Australia Pty Ltd, Australia
2 Novartis
Purpose: We determined the early impact of standardised profiling and anti-hypertensive treatment on early blood pressure (BP) control in hypertensive patients. Methods: The Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) Study, was a prospective, multi-centre randomised controlled trial of a more intensive approach to BP management. We enrolled 2337 patients from 119 primary care clinics with elevated BP with 2185 commencing a standardised “run-in” phase of automated risk profiling and anti-hypertensive therapy (valsartan 80 mg/day for 14–28 days). Results: Overall, 1978 patients (60% men, aged 59 ± 12 years and 61% prior hypertension) completed “run-in”. Initial BP targets were ≤140/90 (41%), ≤130/80 (44%) and ≤125/75 mmHg (15%). Subsequently, 34%, 14% and 7% of patients, respectively, achieved their individual BP target. On an adjusted basis, these patients were more likely to be female (OR 1.43, 95% CI 1.13–1.82; p = 0.003). Alternatively, those with prior hypertension (OR 0.27, 95% CI 0.21–0.35), higher initial systolic (OR 0.96, 95% CI 0.95–0.98 per mmHg) and diastolic (OR 0.97, 95% CI 0.96–0.98 per mmHg) BP and an increasingly stricter BP target (reference group ≤140/90 mmHg, OR 0.24, 95% CI 0.08–0.204 and OR 0.13, 95% CI 0.19–0.31 for the two lower BP targets) were less likely to achieve early BP control. Conclusions: An initial period of profiling and simplified treatment achieved subsequent BP control in almost one in five patients being treated for hypertension. These
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142