Abstract 13502: Statins Buffer the Vasoconstricting, Pro-Inflammatory and Pro-Oxidant Effects of Experimental Venous Congestion in Patients With Systolic Heart Failure on Stable Medical Regimen

Background: In heart failure (HF), statins decrease hospitalizations for acute decompensation, which are primarily due to venous congestion (VC). The reason is unknown. We tested whether statins buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of VC in an established human model of this condition. Methods: We studied 41 pts, NYHA class II-III, LVEF <40%, euvolemic and on stable medical therapy. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of VC. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), and vascular cell adhesion molecule 1 (VCAM-1) were measured by ELISA; isoprostane by LC-MS. Results: Age was 53±2 years, 32% were female, 29% had an ischemic etiology, LVEF was 22±1%, 56% were treated with a statin. Experimental VC increased plasma isoprostane, ET-1, VCAM-1 and IL-6. However, the use of a statin greatly influenced the rate of this response: the increase in isoprostane (marker of oxidative stress) was four-fold higher among nonstatin vs statin users (62.3±11 vs 15.4±11.2 pg/ml, p=0.01); ET-1 (marker of vasoconstriction and inflammation) increased 50% more among nonstatin users (1.83±0.23 vs 1.21±0.21 pg/ml, p=0.05); VCAM-1 (marker of endothelial activation) increased 80% more among non-statin users (62.5±15.1 vs 33.6±13.3 pg/ml, p=0.16). Changes in IL-6 (marker of inflammation) did not differ in the two groups (1.2±.08 vs 1.1±0.08 pg/ml, p=0.78). Of note, the effects of statins on ET-1 was dose-dependent. Conclusions: We provide the first evidence that statins (particularly at high dose) partially buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of experimental VC. Future studies are warranted to address whether short-term high dose statins have an adjunctive role in the treatment of acute decompensation in HF pts.