Magnetic Resonance Imaging Assessment of Vascular Dynamic Function: Correlation Between Endothelial Function and Arterial Stiffness

Variable

Brachial SBP (mmHg)

Abstracts

Exercise

Mean Difference ± S.D.

Intraclass Correlation

P-value

Submaximal

−2.6 ± 11

0.90

<0.001

5.2 ± 18

0.87

<0.001

−0.2 ± 12

0.85

<0.001

4.6 ± 12

0.87

<0.001

0.86

<0.001

Maximal Central SBP (mmHg)

Submaximal Maximal

AIx (%)

Submaximal

−0.8 ± 7 0.3 ± 9.6

0.80

<0.001

−2.7 ± 11

0.82

<0.001

Maximal Brachial PP (mmHg)

Submaximal

1.1 ± 19

0.81

<0.001

Submaximal

−1.6 ± 7.6

0.84

<0.001

Maximal

−0.2 ± 14

0.70

<0.001

Maximal Central PP (mmHg)

doi:10.1016/j.hlc.2007.06.410

406 Lipoprotein (a) is Elevated in Patients with Renovascular Hypertension, but not in Patients with Primary Aldosteronism K. Kostner ∗ , Y. Li, D. Cowly, M. Stowasser School of Medicine, University of Queensland, Brisbane, Australia Background: Lipoprotein (a) {Lp(a)} is one of the most atherogenic lipoproteins and an important risk factor for cardiovascular disease and stroke. Lp(a) has been found to be elevated in hypertensives in several, but not all studies. The reason for this elevation seems unclear. It is also not clear whether Lp(a) is elevated in all forms of hypertension. Since the kidney plays an important role in apo(a) catabolism, we postulated that only patients with renovascular hypertension have elevated plasma Lp(a) levels. Methods: Therefore, we measured Lp(a) levels in two groups of hypertensives: patients with renovascular hypertension (n = 45), and patients with primary aldosteronism (n = 90) and compared them to healthy matched controls (n = 50). Results: Lp(a) plasma levels were significantly elevated in patients with renovascular hypertension (median, 25th, 75th percentiles: 57, 17, 93 mg/dl) when compared to patients with primary aldosteronism (20, 9, 50 mg/dl) and healthy controls (17, 8, 47 mg/dl). Conclusions: Patients with renovascular hypertension, but not patients with primary aldosteronism have elevated Lp(a) levels. Kidney function but not hypertension itself is probably responsible for this elevation of Lp(a). doi:10.1016/j.hlc.2007.06.411

407 Androgens Promote Atherosclerotic Lesions

Calcification

of

S165

Advanced

L. McRobb ∗ , D. Handelsman, A. Heather Heart Research Institute, Camperdown, Sydney, New South Wales, Australia Background: Coronary calcification is an independent risk factor for clinical events. Men have more coronary calcification than women, however, it remains unclear whether this discrepancy reflects estrogen protection in women or androgen-aggravation in men. Methods: Androgen effects on calcification of advanced atherosclerotic lesions were examined using 33-week-old male and female ApoE knockout mice treated with testosterone (T) or dihydrotestosterone (DHT) for 8 weeks. Plaque and calcified area were quantified in fixed and stained sections from the aortic sinus and brachiocephalic artery (BCA). Steroid receptor expression was examined by immunohistochemistry. Results: Calcification increased in response to T treatment in both the sinus and BCA (2.7–4.4-fold, P < 0.05) in both male and female mice. Treatment with the nonaromatisable DHT also increased calcification in the BCA of female and male mice (2.4-fold, P < 0.05), suggesting an androgen-receptor-dependent mechanism. In the sinus, however, DHT treatment decreased calcification (3.7–4.4-fold, P < 0.05) in both genders in association with an up-regulation of estrogen-receptor α and aromatase. Increases in total calcified area occurred despite null (T-treated male mice; <5%, NS) or beneficial effects on lesion size (all other groups; 10–31%, P < 0.05), and despite increases in HDL-C (1.5–1.8-fold, P < 0.01) that were associated with lesion regression. Conclusions: Calcification of atherosclerotic arteries in mice is actively regulated by androgens via classical steroid receptors in a manner independent of lipid levels and rates of plaque formation. Androgen effects on lesion calcification should be further examined to ensure the cardiovascular safety of androgen therapies in men and women. doi:10.1016/j.hlc.2007.06.412 408 Magnetic Resonance Imaging Assessment of Vascular Dynamic Function: Correlation Between Endothelial Function and Arterial Stiffness A.J. Nelson 1,∗ , S.R. Willoughby 1 , J.D. Cameron 2 , C. Piantadosi 1 , S.A. Hope 2 , B.K. Dundon 1 , S.G. Worthley 1 , I.T. Meredith 2 , M.I. Worthley 1 1 Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia; 2 Monash Cardiovascular Research Centre, MonashHeart, Southern Health and Monash University, Melbourne, Australia

Background: Non-invasive measurements of endothelial function and arterial stiffness have been shown to be inde-

ABSTRACTS

Heart, Lung and Circulation 2007;16:S1–S201

S166

Abstracts

Heart, Lung and Circulation 2007;16:S1–S201

ABSTRACTS

pendent predictors of adverse cardiovascular outcomes. However, limited data exists when directly comparing these parameters. Methods: Nineteen healthy volunteers (nine male/ten female) were evaluated. Subjects were fasted and blood taken for hsCRP, glucose, insulin and fasting lipids. Gated MRI (1.5T Siemens Sonata) measurements were determined using a TrueFISP (fast imaging with steady-state free precession) cine sequence with off-line analysis (Image-Pro Plus). Cross-sectional measurements of aorta areas (mm2 ) were undertaken at three separate locations: the ascending (AA), proximal descending (PDA) and distal descending aorta (DDA). Arterial stiffness was evaluated by aortic distensibility [(maximal aortic area − minimal aortic area)/(pulse pressure × minimal aortic area)]. Endothelial-dependent function was evaluated by a brachial flow-mediated dilation technique, with independent function evaluated via sublingual GTN (400 ␮g). Endothelial function was measured via MRI using cross-sectional area and expressed as a percentage of baseline. Results summarised in table below. Results: The mean endothelial-dependent function of the cohort was 16 ± 4% S.E. An inverse correlation was seen with glucose and arterial stiffness and endothelial independent vasodilation. Correlation Coefficient by Kendall’s Tau Test (p-value) AA Endothelial dependent

0.31 (0.06)

PDA

DDA

0.44 (0.009*) 0.43 (0.011*)

Endothelial independent 0.52 (0.002*) 0.56 (0.001*) 0.5 (0.003*)

Conclusion: A significant correlation exists for endothelial function and arterial stiffness. This data suggest that these parameters are mechanistically linked in healthy subjects. doi:10.1016/j.hlc.2007.06.413 409 Ramipril Retards Progression of Aortic Valve Stenosis in Rabbits: Association with Preservation of Nitric Oxide Effects Ngo 1 ,

Stafford 1 ,

Wuttke 1 ,

Doan T.M. Irene Ronald D. Helen Weedon 2 , Malcolm D. Smith 2 , Aaron L. Sverdlov 1 , Jennifer A. Kennedy 1 , John D. Horowitz 1

1 University of Adelaide, Cardiology Unit, The Queen Elizabeth Hospital, Australia; 2 Flinders University, Department of Rheumatology, Repatriation Hospital, Australia

Introduction: We have recently shown that vitamin D2 induces aortic valve stenosis (AVS) in rabbits, with valvular histological/immunohistochemical changes resembling those of human AVS, and with associated endothelial dysfunction as indicated by elevated plasma asymmetric dimethylarginine ([ADMA]) concentration; this therefore represents a convenient model of evolving

AVS. We now evaluate the effects of ramipril for 8 weeks on: (i) AVS development, (ii) nitric oxide (NO) effect in this model. Methods: Rabbits received: (a) vitamin D2 alone (25,000 IU/4 days weekly, (n = 10) or (b) vitamin D2 /ramipril (0.5 mg/kg, n = 12), with six untreated rabbits as normal development comparators. Development of AVS was determined by echocardiographic transvalvular velocity, aortic valve area (AVA), and aortic valve backscatter (AVBS ) (a measure of valvular echogenicity). Endothelial function was assessed by [ADMA] and vasodilator responsiveness to acetylcholine (ACh) in aortic rings; endothelium-independent NO responsiveness was assessed with sodium nitroprusside (SNP). Results: Ramipril retarded the development of AVS (p < 0.05, two-way ANOVA) on both transvalvular velocity and AVA criteria, with some reduction in AVBS (p = 0.08, ttest). Ramipril significantly decreased [ADMA] (p < 0.01, two-way ANOVA); delta [ADMA] and AVBS correlated (r2 = 0.66, p = 0.001). Maximal vascular responses (Emax ) to ACh tended to improve (20.9% versus 46.8%, p = 0.053, Mann–Whitney); with strong correlation between Emax versus AVBS (r2 = 0.9, p < 0.001); Emax to SNP were significantly improved (83 ± 3–92 ± 2%, p = 0.03, unpaired t-test) with ramipril. Conclusions: These data show, for the first time, ACE inhibitor therapy may retard progression of AVS. The strong correlation between AVBS and [ADMA], ACh responses suggest a possible association with preservation of endothelial function/tissue responsiveness to NO. doi:10.1016/j.hlc.2007.06.414 410 Symptomatic Carotid Plaques Recruit High Levels of “Protective” T Regulatory Cells, Apolipoprotein A–I as well as Inflammatory Markers S. Patel 1,2,∗ , S. Bao 3 , S.H. Chung 3 , D.S. Celermajer 1,2 1 Department of Cardiology, Royal Prince Alfred, Hospital, Sydney, Australia; 2 Department of Medicine, University of Sydney, Sydney, Australia; 3 Department of Pathology, University of Sydney, Sydney, Australia

Introduction: Inflammation is important in plaque vulnerability but the precise role of atheroprotective cells and proteins in vulnerable plaque has not been well defined. FoxP3, the major transcription factor for CD4+ /CD25+ regulatory T cells; and apolipoprotein A–I, the chief protein component of high-density lipoproteins, have been implicated in the suppression of inflammation. Our aim was to characterise the expression of these two novel “protective” markers in symptomatic and asymptomatic carotid plaques. Methods: Twenty-two consecutive patients undergoing carotid endartectomy (8 symptomatic and 14 asymptomatic) were stained immunohistochemically for Macrophage Chemotactic Protein 1 (MCP-1), a key inflammatory cytokine; FoxP3 and apolipoprotein A–I. Staining was quantified using Image Pro Plus software. Detailed