Vascular Medicine 2014, Vol. 19(3) 221­–243 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1358863X14533477 vmj.sagepub.com

Society for Vascular Medicine Abstracts Accepted for the 2014 25th Anniversary and Scientific Sessions June 12–14, 2014 La Jolla, California, USA

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Authors will present posters based on the following abstracts at the 2014 SVM 25th Anniversary and Scientific Sessions. The poster session will be at 3:15 p.m., Thursday, June 12, 2014. In honor of Jay D. Coffman (1928–2006), distinguished internist and researcher of vascular medicine and clinical cardiology, SVM sponsors an annual award in vascular medicine and biology research. The top finalists will make oral presentations at the meeting during Session 5: Jay D. Coffman Young Investigator Award Presentations Luncheon, 11:30 a.m., Thursday, June 12, 2014. The winners of the Jay D. Coffman Young Investigator Award (YIA) will be announced during the Award Presentations, 9:15 a.m., Friday, June 13, 2014. All events will take place at the Hilton La Jolla Torrey Pines, La Jolla, California, USA. For more information about the meeting, see the SVM website: www.vascularmed.org/am25 Poster abstracts are organized by category.

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223

SVM Abstracts

Basic science – Vascular medicine

1University

YIA 1 Proton pump inhibitors inhibit the cardiovascular enzyme DDAH and regulate processes underlying idiopathic pulmonary fibrosis

Yohannes T Ghebremariam1, Qingtao Zhou2, Joao de Andrade3, Lawrence Ho4, Glenn D Rosen4, John P Cooke1 1Houston Methodist Research Institute, Houston, TX, USA; 2Peking University Third Hospital, Beijing, China; 3University of Alabama at Birmingham, Birmingham, AL, USA; 4Stanford University, Stanford, CA, USA

Rationale: The cardiovascular enzyme dimethylarginine dimethylaminohydrolase (DDAH) has recently been implicated in the progression of idiopathic pulmonary fibrosis (IPF). By degrading asymmetric dimethylarginine (ADMA), an endogenous inhibitor of inducible nitric oxide (NO) synthase (iNOS), DDAH releases the brake on a pathway implicated in lung injury and fibrosis. Objectives: To discover DDAH inhibitors, and to assess the effect of such inhibitors on processes underlying IPF. Methods: We performed high throughput screening (HTS) of over 130,000 small molecules and discovered that the proton pump inhibitors (PPIs) directly inhibit DDAH. In addition, we assessed the effect of PPIs on collagen synthesis by IPF lung fibroblasts. Finally, retrospective analysis of interstitial lung disease (ILD) database was performed to assess the effect of PPIs on transplant-free survival of IPF patients. Results: We found that the PPIs inhibit DDAH activity in biochemical assays, cell culture and in vivo. In addition, the PPIs reduced the production of soluble collagen by primary IPF lung fibroblasts in response to the pro-fibrotic cytokine TGFβ and regulated both proliferation and survival of lung alveolar epithelial cells. Retrospective review of the ILD database of 215 IPF patients (of who 130 were on PPIs for >1 year) revealed a survival advantage (i.e. time to transplant or death when calculated from the time of diagnosis) of the patients on PPIs compared to controls. Conclusions: Our data reveal a plausible biological explanation for the clinical benefit of the PPIs in IPF. The reported reduction in radiologic fibrosis score and survival advantage of IPF patients on PPIs may be due to modulation of the DDAH/NOS pathway.

Clinical science/epidemiology – Arterial and aortic disease

of Colorado, Denver, CO, USA; 2University of California, Davis, Sacramento, CA, USA Background: Angiotensin converting enzyme inhibitors (ACEI) are recommended for secondary prevention in peripheral arterial disease, but their effectiveness in patients with critical limb ischemia (CLI) is uncertain. Methods: Four hundred and fourteen patients (177 women, 237 men) with CLI underwent diagnostic angiography or therapeutic endovascular intervention from 2006 to 2012 at a multidisciplinary vascular center. ACEI or angiotensin receptor blocker use was assessed at the time of angiography and confirmed during the follow-up period. Major adverse cardiovascular events (MACE), mortality, and major adverse limb events (MALE) were assessed during a 3-year follow-up. Propensity matching was used to adjust for baseline differences between patients taking and not taking ACEI. Results: 234 (57%) patients were prescribed ACEI. Patients prescribed ACEI had more baseline comorbidities including diabetes (70% vs 53%, p=0.001) and hypertension (94% vs 72%, p=0.001). Patients prescribed ACEI had lower 3-year unadjusted rates of MACE (40% vs 46%), mortality (34% vs 42%), and major amputation (18% vs 23%). After propensity matching, ACEI use was associated with significantly lower rates of MACE (HR 0.76, 95% CI 0.58–0.99) and overall mortality (HR 0.71, 95% CI 0.53–0.95). There was no significant association between ACEI use and MALE (HR 0.77, 95% CI 0.58– 1.03) or major amputation. Conclusions: ACEI use is associated with lower MACE and mortality in patients with CLI, but no effect on limbrelated outcomes.

Figure.

YIA 3

YIA 2 Fibromuscular dysplasia is a morbid disease with low associated mortality: A report of Association between angiotensin converting the United States Registry for Fibromuscular enzyme inhibitor use and major adverse Dysplasia cardiovascular events among patients with Sarah O’Connor1, Jeffrey W Olin2, Xiaokui Gu3, J Michael critical limb ischemia Bacharach4, Yung-Wei Chi5, James Froehlich3, Bruce Gray6,

Ehrin J Armstrong1, Debbie C Chen2, Gagan D Singh2, Ezra A Amsterdam2, John R Laird2

Esther SH Kim7, Eva Kline-Rogers3, Pamela Mace8, Robert McBane9, Aditya Sharma10, Heather Gornik7

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224

Vascular Medicine 19(3)

1Cleveland

Clinic Lerner College of Medicine, Cleveland, OH, USA; 2Mount Sinai School of Medicine, New York, NY, USA; 3University of Michigan, Ann Arbor, MI, USA; 4North Central Heart, Sioux Falls, SD, USA; 5University of California, Davis, Sacramento, CA, USA; 6Vascular Health Alliance, Greenville, SC, USA; 7Cleveland Clinic Foundation, Cleveland, OH, USA; 8Fibromuscular Dysplasia Society of America, Rocky River, OH, USA; 9Mayo Clinic, Rochester, MN, USA; 10University of Virginia Health System, Charlottesville, VA, USA Background: Fibromuscular dysplasia (FMD) is an uncommon non-atherosclerotic disease of medium sized arteries. The natural history of this disease remains unknown. Methods: Prevalence of major vascular events at the time of enrollment and during initial Registry follow-up are reported. Major vascular event was defined as: death, dissection, MI, coronary revascularization, TIA, stroke, SAH, mesenteric ischemia, or renal infarction. Results: Among 913 patients, mean age at enrollment was 55.9±12.8 years (range 18–90), and 91.9% were female. 38.1% of patients had at least one major vascular event at the time of enrollment (Table). 23.7% (207/873) of patients had ≥1 arterial dissection and 23.1% (201/871) had ≥1 aneurysm. Median follow-up for 488 patients who were enrolled ≥1 year and with ≥1 follow-up visit was 23.9 months (IQR 12.4–36.3). During follow-up, 29 major vascular events occurred in 22 patients at a rate of 2.9 events per 100 patient-years (Table). There was no significant difference in the risk of subsequent major vascular event between groups with and without prior vascular events, HR=1.2 (95% CI 0.5–3.2; p=0.71). There were 4 deaths (0.8%), 3 of which were due to malignancy and 1 of unknown cause. Conclusions: FMD is a morbid vascular disease associated with a high rate of major vascular events but low mortality (Table). While many FMD patients present with dissection, stroke, or infarction, few proceed to have further vascular complications during surveillance. There is no evidence that history of a major vascular event was associated with increased risk of subsequent events during the first 2 years of follow-up. Table. Distribution of vascular events at baseline and follow-up.

Baseline

Event type

No. of patients (%)

Any major event Dissection TIA Stroke MI or coronary revascularization Renal infarction SAH Mesenteric ischemia Death Aneurysm

348/913 (38.1) 207/873 (23.7) 111/868 (12.8) 91/876 (10.4) 36/847 (4.3) 27/605 (4.5) 20/838 (2.4) 13/826 (1.6) 0/913 (0) 201/871 (23.1) (Continued)

Table. Continued

Follow-up

Event type

No. of patients (%)

Any major event Death Dissection MI or coronary revascularization TIA Stroke SAH Mesenteric ischemia Renal infarction Renal failure Amaurosis fugax New headache

22/488 (4.5) 4/488 (0.8) 7/488 (1.4) 6/488 (1.2) 5/488 (1.0) 2/488 (0.4) 1/488 (0.2) 1/488 (0.2) 0/488 (0) 3/488 (0.6) 4/488 (0.8) 30/488 (6.1)

Clinical science/epidemiology – Other YIA 4 Registry findings of fibromuscular dysplasia of the mesenteric arteries

Erin K Moore1, Xiaokui Gu2, Jeffrey W Olin3, James B Froehlich2, J Michael Bacharach4, Michael R Jaff5, Barry T Katzen6, Eva Kline-Rogers2, Pamela D Mace7, Alan H Matsumoto8, Robert D McBane9, Christopher J White10, Esther SH Kim11, Heather L Gornik11, Bruce H Gray1 1Greenville Health System, Greenville, SC, USA; 2University of Michigan, Ann Arbor, MI, USA; 3Mount Sinai Medical Center, New York, NY, USA; 4North Central Heart, Sioux Falls, SD, USA; 5Massachusetts General Hospital, Boston, MA, USA; 6Miami Baptist Cardiac/Vascular Institute, Miami, FL, USA; 7Fibromuscular Dysplasia Society of America, Rocky River, OH, USA; 8University of Virginia Health System, Charlottesville, VA, USA; 9Mayo Clinic, Rochester, MN, USA; 10Ochsner Clinic, New Orleans, LA, USA; 11Cleveland Clinic Foundation, Cleveland, OH, USA Introduction: Fibromuscular dysplasia (FMD) most commonly affects the renal, carotid and vertebral arteries. The prevalence and natural history of mesenteric arterial FMD (mFMD) is unknown. Methods: Data from the United States Registry for Fibromuscular Dysplasia was collected from the registry for patients who had assessment of their mesenteric arteries and compared to those with renal, carotid and/or vertebral artery FMD. Prevalence, demographics (including history and physical examination), other vascular beds involved, and interventions performed were compared with patients who had no mesenteric involvement. Results: Of 873 patients in the registry, 492 (56.4%) patients had their mesenteric vessels imaged. 95 (19.3%) had involvement of their mesenteric arteries (mFMD). Of the 95 mFMD patients, 15 (15.8%) were male. Compared to the patients without mFMD, they were younger (49.4±12.4 vs 52.6±13.0, p=0.016) and often present with abdominal complaints, like post prandial abdominal pain (18.8% vs 6.5%, p=0.001), flank or abdominal pain (34.9% vs 17.7%), abdominal bruit (30.5% vs 7.8%, p