Abstract: SA-PO341
Mechanisms for Increased Cardiovascular Risk in Patients with ANCA Vasculitis in Long-Term Remission
Session Information
- Hypertension and CVD: Mechanisms
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Author
- Farrah, Tariq E., University of Edinburgh, Edinburgh, United Kingdom
Background
Current treatments have improved the short-term survival of patients with ANCA-associated vasculitis (AAV), an autoimmune disease that often involves the kidneys. Long-term outcomes remain poor due to an increased risk of cardiovascular disease (CVD). AAV is defined by systemic endothelial injury but few clinical studies have robustly explored endothelial dysfunction as a contributor to CVD risk in these patients. We assessed brachial artery vasodilation and release of tissue plasminogen activator (tPA, an endogenous thrombolytic) as measures of endothelial function that predict CVD.
Methods
We recruited 32 AAV patients in long-term remission and 32 age- and sex-matched healthy controls into a prospective cohort study. Those with renal impairment, proteinuria, diabetes and overt CVD were excluded. Vasodilation was assessed by gold standard forearm blood flow during randomized intra-arterial infusions of acetylcholine (ACh, endothelium-dependent vasodilator, 7.5/15/30µg/min) and sodium nitroprusside (SNP, endothelium-independent vasodilator, 2/4/8µg/min). tPA release was measured during intra-arterial bradykinin (100/300/1000pmol/min).
Results
AAV patients had a mean±SD age of 55±13 years and 23 (72%) were male. The median (range) time from diagnosis was 4 (1-13) years and 17 (53%) were PR3+. 22 (69%) patients were prescribed a renin-angiotensin system blocker, and 21 (66%) were receiving a statin or ezetimibe.
Forearm blood flow increased dose-dependently during all infusions. AAV patients had reduced ACh-mediated vasodilation compared to controls (p<0.01 at peak dose, ~25% difference in area under the curve). Responses to SNP did not differ.
Compared to controls, AAV patients had lower mean±SD tPA release (125±50 vs 65±52 ng/100ml/min at peak dose, p<0.001). tPA release was lower in PR3+ vs MPO+ patients (52±40 vs 90±70 ng/100ml/min, p<0.05), and in patients on maintenance immunosuppression compared to those on no immunosuppression (91±43 vs 54±50 ng/100ml/min, p<0.01), who had similar tPA release to controls.
Conclusion
AAV patients in long-term remission have significant endothelial dysfunction, comparable to that seen following myocardial infarction or in advanced CKD; this may partly explain their increased CVD risk. Targeting these with existing and novel therapies may improve long-term outcomes in AAV.