Sex-based Differences in the Pattern of Hypertension-related Heart Disease in a Black African Urban...

2
ABSTRACTS Heart, Lung and Circulation Abstracts S21 2008;17S:S1–S209 47 Altered Angiotensin II Receptor Expression and Dispo- sition of Circulating Progenitor Cells in Thoracic Aortic Aneurysm Malcolm West 1,, M. Sata 2 , D. Fukuda 2 , Jennifer West 1 , Maria Nataatmadja 1 1 University of Queensland, Prince Charles Hospitals, Brisbane, Australia; 2 Tokyo University School of Medicine, Tokyo, Japan We hypothesised that in human thoracic aortic aneurysm associated with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) abnormal expression of angiotensin II (AngII) receptors leads to changes in disposition of circu- lating vascular progenitor cells (CPCs) and adverse effects on tissue remodelling. Expression of AngII type 1 and type 2 receptors (AT1R, AT2R) and disposition of CPCs were compared in MFS and BAV aneurysm and in an ApoE/mouse aneurysm model. Tissue from subjects with MFS (three males, two females; 28–67 years) and BAV (three males, two females; 53–73 years) and normal tho- racic aorta from organ donor subjects (two males, three females; 27–72 years) were collected. Female 5-month-old ApoE/mice transplanted with green fluorescent pro- tein (GFP)+/+ ApoE/bone marrow were infused with AngII for 2 weeks. In MFS and BAV abnormal AT1R and AT2R expression and CD34+ CPCs were detected in areas of intimal thickening. There was expression of AT1R, AT2R and occasional CD34+ cells in media and adventitia. In the animal model AngII resulted in either thoracic aortic dissection (29%) or significant intimal thickening (71%). GFP+ CPCs were found in cells forming intimal thickening in thoracic and abdominal aorta. Increased accumulation of GFP+ cells was found in adventitia corresponding to areas of intimal thickening. Aortic dissection was present in regions of the aorta without intimal thickening and without adventitial GFP+ cells. The study suggests altered AT1R and AT2R regulation affects CPC disposition and vascular wall remodelling. Absence of intimal and adven- titial CPCs was a precursor for aneurysm development and dissection. doi:10.1016/j.hlc.2008.05.048 48 Over-expression of Matrix Metalloproteinase-10 is Asso- ciated with Vascular Smooth Muscle Cell loss in Marfan Syndrome and Bicuspid Aortic Valve Aneurysm Hong Lien Do , Maria Nataatmadja, Malcolm West University of Queensland, Prince Charles Hospital, Brisbane, Australia Thoracic aortic aneurysm associated with Marfan syn- drome (MFS) or bicuspid aortic valve (BAV) is charac- terized by over-expression of matrix metalloproteinases (especially MMP-2 and MMP-9). Up-regulated MMP-10 has been linked to reduced cell–matrix interaction, cell detachment, dilation and rupture of blood vessels. We investigated MMP-10 expression in aortic aneurysm tissue and cultured VSMCs and its relation to VSMC apopto- sis. Aortic tissue and cultured VSMCs were derived from subjects with MFS (five males, two females; 40 ± 22 years, mean ± S.D.) and BAV (five males, two females; 60 ± 16 years), and normal subjects (three males, six females; 44 ± 14 years). Caspase-3 was used as a marker of cells undergoing apoptosis. Specific staining of aortic tissue showed increased expression of MMP-10 in MFS and BAV (P < 0.05). Similar results were obtained in cultured VSMCs. In VSMCs characterized by cell shrinkage of cell and nuclear condensation there was enhanced staining of MMP-10. The same VSMCs showed caspase-3 labelling in alternate serial sections. The proportion of apoptotic VSMCs in aneurysm tissue was significantly increased in the aneurysm wall of patient groups compared to normal subjects (P < 0.05). Gelatin zymography showed no active form of MMP-10 and Western blot indicated the presence of the MMP-10 pro-form only with higher levels of expres- sion in VSMC conditioned media from patients compared to normals (P < 0.05). The study suggests that expression of MMP-10 is related to progression of aortic wall aneurysm in MFS and BAV. doi:10.1016/j.hlc.2008.05.049 CARDIAC DISEASE – SOCIAL ASPECTS 49 Sex-based Differences in the Pattern of Hypertension- related Heart Disease in a Black African Urban Commu- nity: The Heart of Soweto Study Simon Stewart 1,2,, Elena Libhaber 1,2 , Melinda Carrington 1,2 , Karen Sliwa 1,2 1 Baker Heart Research Institute, Melbourne, Australia; 2 University of Witwatersrand, Johannesburg, South Africa Background: The Heart of Soweto Study is the largest study of emergent heart disease (HD) in Africa. Methods: Baragwanath Hospital in Soweto provides health care to a population of 1.1 million mainly black Africans. We registered detailed demographic, clinical and diagnostic data from all de novo presentations of heart disease (HD) in 2006.Results: In 2006, 761 “de novo” black African patients presented with hypertension (HT). Women predominated (68%) but were aged similar to men (59 ± 15 years). Mean systolic/diastolic blood pres- sures (BPs) were 137 ± 28/77 ± 17 mm Hg with minimal sex-based differences. Established forms of HD were com- mon: heart failure (HF, 54%), valvular HD (17%), renal disease (9%) and CAD (6%). Women were more obese (OR 2.66, 95% CI 1.83–3.86), symptomatic (OR 1.23, 95% CI 1.12–1.34), had more valvular HD (OR 1.42, 95% CI 1.00–2.03) but less HF (OR 0.85, 95% CI 0.30–0.73) or renal disease (OR 0.47, 95% CI 0.30–0.73). Men had a lower left ventricular ejection fraction (LVEF, 51 ± 18% vs. 57 ± 16%; p < 0.001). In both sexes increasing age (R = 0.142, p < 0.0001) and a higher LVEF (R = 0.167, p < 0.0001) was cor- related with systolic BP. In men only, increasing BMI was correlated with systolic (R = 0.245, p = 0.006) and diastolic BP (R = 0.225, p = 0.012).

Transcript of Sex-based Differences in the Pattern of Hypertension-related Heart Disease in a Black African Urban...

AB

ST

RA

CT

S

Heart, Lung and Circulation Abstracts S212008;17S:S1–S209

47Altered Angiotensin II Receptor Expression and Dispo-sition of Circulating Progenitor Cells in Thoracic AorticAneurysm

Malcolm West 1,∗, M. Sata 2, D. Fukuda 2, Jennifer West 1,Maria Nataatmadja 1

1 University of Queensland, Prince Charles Hospitals, Brisbane,Australia; 2 Tokyo University School of Medicine, Tokyo, Japan

We hypothesised that in human thoracic aortic aneurysmassociated with Marfan syndrome (MFS) and bicuspidaortic valve (BAV) abnormal expression of angiotensin II(AngII) receptors leads to changes in disposition of circu-lating vascular progenitor cells (CPCs) and adverse effectson tissue remodelling. Expression of AngII type 1 andtype 2 receptors (AT1R, AT2R) and disposition of CPCswere compared in MFS and BAV aneurysm and in anApoE−/− mouse aneurysm model. Tissue from subjectswith MFS (three males, two females; 28–67 years) and BAV(three males, two females; 53–73 years) and normal tho-racic aorta from organ donor subjects (two males, threefemales; 27–72 years) were collected. Female 5-month-oldApoE−/− mice transplanted with green fluorescent pro-tein (GFP)+/+ ApoE−/− bone marrow were infused withAngII for 2 weeks. In MFS and BAV abnormal AT1R andAT2R expression and CD34+ CPCs were detected in areasof intimal thickening. There was expression of AT1R, AT2RatdGioaiwAvtd

d

4OcS

H

A

Tdt(hdia

sis. Aortic tissue and cultured VSMCs were derived fromsubjects with MFS (five males, two females; 40 ± 22 years,mean ± S.D.) and BAV (five males, two females; 60 ± 16years), and normal subjects (three males, six females;44 ± 14 years). Caspase-3 was used as a marker of cellsundergoing apoptosis. Specific staining of aortic tissueshowed increased expression of MMP-10 in MFS andBAV (P < 0.05). Similar results were obtained in culturedVSMCs. In VSMCs characterized by cell shrinkage of celland nuclear condensation there was enhanced staining ofMMP-10. The same VSMCs showed caspase-3 labellingin alternate serial sections. The proportion of apoptoticVSMCs in aneurysm tissue was significantly increased inthe aneurysm wall of patient groups compared to normalsubjects (P < 0.05). Gelatin zymography showed no activeform of MMP-10 and Western blot indicated the presenceof the MMP-10 pro-form only with higher levels of expres-sion in VSMC conditioned media from patients comparedto normals (P < 0.05). The study suggests that expression ofMMP-10 is related to progression of aortic wall aneurysmin MFS and BAV.

doi:10.1016/j.hlc.2008.05.049

CARDIAC DISEASE – SOCIAL ASPECTS

49Sex-based Differences in the Pattern of Hypertension-rn

SC

1

2

BsMhAahbWmssmd(C1rl5prcB

nd occasional CD34+ cells in media and adventitia. Inhe animal model AngII resulted in either thoracic aorticissection (29%) or significant intimal thickening (71%).FP+ CPCs were found in cells forming intimal thickening

n thoracic and abdominal aorta. Increased accumulationf GFP+ cells was found in adventitia corresponding toreas of intimal thickening. Aortic dissection was presentn regions of the aorta without intimal thickening and

ithout adventitial GFP+ cells. The study suggests alteredT1R and AT2R regulation affects CPC disposition andascular wall remodelling. Absence of intimal and adven-itial CPCs was a precursor for aneurysm development andissection.

oi:10.1016/j.hlc.2008.05.048

8ver-expression of Matrix Metalloproteinase-10 is Asso-

iated with Vascular Smooth Muscle Cell loss in Marfanyndrome and Bicuspid Aortic Valve Aneurysm

ong Lien Do ∗, Maria Nataatmadja, Malcolm West

University of Queensland, Prince Charles Hospital, Brisbane,ustralia

horacic aortic aneurysm associated with Marfan syn-rome (MFS) or bicuspid aortic valve (BAV) is charac-

erized by over-expression of matrix metalloproteinasesespecially MMP-2 and MMP-9). Up-regulated MMP-10as been linked to reduced cell–matrix interaction, celletachment, dilation and rupture of blood vessels. We

nvestigated MMP-10 expression in aortic aneurysm tissuend cultured VSMCs and its relation to VSMC apopto-

elated Heart Disease in a Black African Urban Commu-ity: The Heart of Soweto Study

imon Stewart 1,2,∗, Elena Libhaber 1,2, Melindaarrington 1,2, Karen Sliwa 1,2

Baker Heart Research Institute, Melbourne, Australia;University of Witwatersrand, Johannesburg, South Africa

ackground: The Heart of Soweto Study is the largesttudy of emergent heart disease (HD) in Africa.

ethods: Baragwanath Hospital in Soweto providesealth care to a population of 1.1 million mainly blackfricans. We registered detailed demographic, clinicalnd diagnostic data from all de novo presentations ofeart disease (HD) in 2006.Results: In 2006, 761 “de novo”lack African patients presented with hypertension (HT).omen predominated (68%) but were aged similar toen (59 ± 15 years). Mean systolic/diastolic blood pres-

ures (BPs) were 137 ± 28/77 ± 17 mm Hg with minimalex-based differences. Established forms of HD were com-on: heart failure (HF, 54%), valvular HD (17%), renal

isease (9%) and CAD (6%). Women were more obeseOR 2.66, 95% CI 1.83–3.86), symptomatic (OR 1.23, 95%I 1.12–1.34), had more valvular HD (OR 1.42, 95% CI.00–2.03) but less HF (OR 0.85, 95% CI 0.30–0.73) orenal disease (OR 0.47, 95% CI 0.30–0.73). Men had aower left ventricular ejection fraction (LVEF, 51 ± 18% vs.7 ± 16%; p < 0.001). In both sexes increasing age (R = 0.142,< 0.0001) and a higher LVEF (R = 0.167, p < 0.0001) was cor-

elated with systolic BP. In men only, increasing BMI wasorrelated with systolic (R = 0.245, p = 0.006) and diastolicP (R = 0.225, p = 0.012).

AB

ST

RA

CT

S

S22 Abstracts Heart, Lung and Circulation2008;17S:S1–S209

Conclusions: These unique data confirm the importanceof HT as a precursor to advanced forms of HD in urbanblack Africans.

doi:10.1016/j.hlc.2008.05.050

50Prevalence of Obesity and Hypertension in Urban andRural Communities: A Comparison of South African andAustralian Risk Factor Prevalence Data

Melinda Carrington 1,2,∗, Simon Stewart 1,2, KemiTibazarwa 1,2, Karen Sliwa 1,2

1 Baker Heart Research Institute, Melbourne, Australia;2 University of the Witwatersrand, Johannedsburg, South Africa

Purpose: The same key risk factors have driven an epi-demic of cardiovascular disease (CVD) in “developed”countries and will likely drive a future epidemic of CVD in“developing” countries undergoing epidemiologic transi-tion.Methods: We recently screened a total of 1127 blackAfricans in urban Soweto (Urban-RSA) for common riskfactors for CVD. Using the same methods in Australiaas part of a National Blood Pressure Screening Day, werecently screened 10,649 and 3038 participants in urban(Urban-Aus) and rural (Rural-Aus) communities (pre-dominantly Caucasian) for the same risk factors.

51A Broad Spectrum of Heart Disease and Risk Factors ina Black Urban Population in South Africa: The Heart ofSoweto Study

Simon Stewart 1,2,∗, Lucas Ntyintyane 1,2, KemiTibazarwa 1,2, Anthony Becker 1,2, Karen Sliwa 1,2

1 Baker Heart Research Institute, Melbourne, Australia;2 University of Witwatersrand, Johannesburg, South Africa

Background: The Heart of Soweto Study is the largeststudy of emergent heart disease in Africa to date.Methods: Baragwanath Hospital in Soweto provideshealth care to a population of 1.1 million mainly blackAfricans. We registered detailed demographic, clinicaland diagnostic data from all de novo presentations of heartdisease (HD) in 2006.Results: There were 1593 de novo presentations for mainlyadvanced HD. Black Africans (85%) and women predom-inated (60%); being slightly younger than men (53 ± 16years vs. 55 ± 15 years: p = 0.031). Risk factor prevalencewas high (56% had hypertension) with >60% having mul-tiple risks. Heart failure (HF) was the most commonprimary diagnosis (44%) with systolic dysfunction evidentin 53% of cases and 66% attributable to dilated cardiomy-opathy and/or hypertensive HD. Other common primarydiagnoses were hypertension (19%), valvular HD (17%)and coronary artery disease (CAD, 10%). Within a large

Results: Median (IQR) age of participants in Urban-RSA,Urban-Aus, and Rural-Aus was 45 (IQR 34–55) years, 48(36–59) years and 51 (39–62) years. The proportion ofwomen in Urban-RSA, Urban-Aus, and Rural-Aus was63%, 55% and 57%, respectively. In Urban-RSA, 23% ofmen and 51% of women were obese (BMI ≥ 30 kg/m2)versus 25% and 26%, and 33% and 33% of men andwomen respectively living in Urban-Aus and Rural-Aus.Overall, 30% of men (median BP 130/80 mmHg) and 31%of women (BP 130/81) in Urban-RSA were hypertensive(systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg)compared to 41% of men (134/81 mmHg) and 25% ofwomen (125/77 mmHg) in Urban-Aus and 49% of men(137/82 mmHg) and 34% of women (130/79 mmHg) inRural-Aus.Summary: These data confirm high levels of risk in allthree target communities with some potentially importantdifferences that will require potentially different publichealth initiatives.

doi:10.1016/j.hlc.2008.05.051

infective component, comorbity included anaemia (13%),diabetes (10%) and renal dysfunction (10%). More blackAfricans presented in HF (54% vs. 45% – OR 2.36, 95%CI 1.74–3.21: p < 0.0001); alternatively, less presented withCAD (6% vs. 38% – OR 0.10, 95% CI 0.07–0.14: p < 0.0001).Similarly, women were more likely to present with valvu-lar HD than men (26% vs. 18% – OR 1.30, 95% CI 1.11–1.52:p = 0.0001).Summary: We found multiple threats to the current andfuture heart health of Soweto, South Africa.

doi:10.1016/j.hlc.2008.05.052

52Hospital Length of Stay in Patients Undergoing Percuta-neous Coronary Intervention

Nick Andrianopoulos 1,∗, Stephen J. Duffy 2, Angela L.Brennan 1, Gishel New 3, Andrew E. Ajani 4, David J.Clark 5, Nino Hay 1, Douglas Wong 1, Zahide Yildirim 1,Christopher Reid 1

1 Monash Centre of Cardiovascular Research & Educationin Therapeutics, Monash University, Melbourne, Australia;2 Alfred Hospital, Melbourne, Australia; 3 Box Hill Hospital,Melbourne, Australia; 4 Royal Melbourne Hospital, Melbourne,Australia; 5 Austin Hospital, Melbourne, Australia

Background: Coronary heart disease treatment results inthe highest direct expenditure on any individual diseasein Australia (2000-2001 AIHW data), and over 70% of thisbudget is spent on inpatient hospital care. An apprecia-ble proportion of this is due to percutaneous coronaryintervention (PCI), and the length of stay (LOS) for these