Anxiety is the most common psychiatric disorder. Anxiety is associated with increased risk of cardiovascular events, independent of conventional risk factors. However, the mechanisms underiying this link are unknown, and it has never been proved that treating anxiety reduces cardiovascular risk. This project will address these important issues. We have gathered compelling data demonstrating that even modest anxiety symptoms are associated with sympathetic nerve activation, inflammation, and profound impairment of resistance vessel function in humans. Using a multidisciplinary approach, we will address three speciflc aims: 1) Does anxietv produce vascular dvsfunction through increased inflammation or oxidant stress? We will measure ex vivo endothelial cell proteins reflecting inflammation and oxidant stress in subjects with anxiety symptom scores in the highest and lowest quartiles. We will then test whether anti-inflammatory (salsalate) and anti-oxidant (ascorbic acid) interventions reverse vascular dysfunction in high compared to low anxiety subjects.
This aim will additionally examine whether peripheral resistance vessel dysfunction is also present in the brain using functional MRI to measure cerebral blood flow, and whether this is improved by salsalate. 2) Does anxietv produce vascular dysfunction through svmpathetic activation? We will test whether sympathetic inhibition with clonidine for 4 weeks improves inflammation, oxidant stress and vascular dysfunction to a greater degree in high than low anxiety subjects. 3) Does treatment of anxietv improve svmpathetic activation, inflammation, oxidant stress and Vascular dvsfunction? We will randomly assign subjects with high anxiety to a novel mindfulness-based acceptance and commitment therapy (ACT) or time control. This therapy has been shown in our hands and others to have substantial and durable effects on anxiety symptoms. We will test whether ACT produces signiflcantly greater improvements in microneurographic sympathetic nerve activity, endothelial cell proteins reflecting inflammation and oxidant stress, and forearm resistance vessel function. This project should: A) Provide compelling evidence that anxiety causes vascular damage. B) Elucidate mechanisms involved in the effects of anxiety on the vasculature. C) Help develop novel phenotypes for future research on anxiety classiflcation, severity and treatment. D) Suggest new strategies for cardiovascular risk stratiflcation and prevention. We will achieve these goals through a distinctive multidisciplinary collaboration between investigators expert in cardiovascular biology, psychiatry, behavioral psychology and neuroimaging.
Anxiety is a psychiatric condition found in about 20% ofthe US population, which has been linked to increased risk for heart attack and stroke. We propose to examine the reasons for this association, and test agents that block inflammation and the sympathetic nervous system in patients with low and high levels of anxiety. We will also examine whether treating anxiety reduces sympathetic activation and vascular damage. This project will help develop new ways to identify and treat people at high cardiovascular risk.
|Xue, Baojian; Thunhorst, Robert L; Yu, Yang et al. (2016) Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension. Hypertension 67:163-70|
|Pierce, Gary L; Kalil, Graziela Z; Ajibewa, Tiwaloluwa et al. (2016) Anxiety independently contributes to elevated inflammation in humans with obesity. Obesity (Silver Spring) :|
|Chu, Yi; Lund, Donald D; Doshi, Hardik et al. (2016) Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice. Arterioscler Thromb Vasc Biol 36:466-74|
|Littlejohn, Nicole K; Keen, Henry L; Weidemann, Benjamin J et al. (2016) Suppression of Resting Metabolism by the Angiotensin AT2 Receptor. Cell Rep 16:1548-60|
|Pierce, G L; Harris, S A; Seals, D R et al. (2016) Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise. J Hum Hypertens 30:513-20|
|Harwani, Sailesh C; Ratcliff, Jason; Sutterwala, Fayyaz S et al. (2016) Nicotine Mediates CD161a+ Renal Macrophage Infiltration and Premature Hypertension in the Spontaneously Hypertensive Rat. Circ Res 119:1101-1115|
|Chapleau, Mark W; Rotella, Diane L; Reho, John J et al. (2016) Chronic vagal nerve stimulation prevents high-salt diet-induced endothelial dysfunction and aortic stiffening in stroke-prone spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 311:H276-85|
|Fiedorowicz, Jess G; Dantz, Bezalel; Blazek, Mary C (2016) Attitudes and Confidence in the Integration of Psychiatry Scale. Acad Psychiatry 40:218-23|
|Sabharwal, Rasna; Rasmussen, Lynn; Sluka, Kathleen A et al. (2016) Exercise prevents development of autonomic dysregulation and hyperalgesia in a mouse model of chronic muscle pain. Pain 157:387-98|
|Xue, Baojian; Yu, Yang; Zhang, Zhongming et al. (2016) Leptin Mediates High-Fat Diet Sensitization of Angiotensin II-Elicited Hypertension by Upregulating the Brain Renin-Angiotensin System and Inflammation. Hypertension 67:970-6|
Showing the most recent 10 out of 140 publications