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The mechanisms underlying this increased risk are not known.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat\u2010related and non\u2010combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Post\u2010traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat\u2010related PTSD were compared with 14 matched Controls without PTSD.\u00a0 Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress:\u00a0 combat\u2010related mental stress using virtual reality combat exposure (VRCE) and non\u2010combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD <jats:italic>vs<\/jats:italic>. Controls, MSNA (+8.2\u00a0\u00b1\u00a01.0\u00a0<jats:italic>vs<\/jats:italic>. +1.2\u00a0\u00b1\u00a01.3\u00a0bursts\u00a0min<jats:sup>\u20131<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and heart rate responses (+3.2\u00a0\u00b1\u00a01.1\u00a0<jats:italic>vs<\/jats:italic>. \u22122.3\u00a0\u00b1\u00a01.0\u00a0beats\u00a0min<jats:sup>\u20131<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) were significantly augmented during VRCE.\u00a0 Similarly, in PTSD <jats:italic>vs<\/jats:italic>. Controls, MSNA (+21.0\u00a0\u00b1\u00a02.6\u00a0<jats:italic>vs<\/jats:italic>. +6.7\u00a0\u00b1\u00a01.5\u00a0bursts\u00a0min<jats:sup>\u20131<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and diastolic BP responses (+6.3\u00a0\u00b1\u00a01.0\u00a0<jats:italic>vs<\/jats:italic>. +3.5\u00a0\u00b1\u00a01.0\u00a0mmHg, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.011) were significantly augmented during MA but not during CPT (<jats:italic>P<\/jats:italic>\u00a0=\u00a0not significant). In the PTSD group, sympathetic BRS (\u20131.2\u00a0\u00b1\u00a00.2\u00a0<jats:italic>vs<\/jats:italic>. \u20132.0\u00a0\u00b1\u00a00.3\u00a0burst incidence\u00a0mmHg<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.026) and cardiovagal BRS (9.5\u00a0\u00b1\u00a01.4\u00a0<jats:italic>vs<\/jats:italic>. 23.6\u00a0\u00b1\u00a04.3\u00a0ms\u00a0mmHg<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive\u2010C\u2010reactive protein levels compared to Controls (2.1\u00a0\u00b1\u00a00.4\u00a0<jats:italic>vs<\/jats:italic>. 1.0\u00a0\u00b1\u00a00.3\u00a0mg\u00a0L<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.047). Augmented SNS and haemodynamic responses to mental stress, blunted\u00a0BRS and inflammation may contribute to an increased CV risk in PTSD.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274269","type":"journal-article","created":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T00:58:38Z","timestamp":1494809918000},"page":"4893-4908","source":"Crossref","is-referenced-by-count":125,"title":["Baroreflex dysfunction and augmented sympathetic nerve responses during mental stress in veterans with post\u2010traumatic stress disorder"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-9172","authenticated-orcid":false,"given":"Jeanie","family":"Park","sequence":"first","affiliation":[{"name":"Renal Division Department of Medicine Emory University School of Medicine  Atlanta GA USA"},{"name":"Research Service Line Atlanta VA Medical Center  Decatur GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Marvar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Institute for Neuroscience George Washington University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhou","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Rollins School of Public Health Emory University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie L.","family":"Kankam","sequence":"additional","affiliation":[{"name":"Renal Division Department of Medicine Emory University School of Medicine  Atlanta GA USA"},{"name":"Research Service Line Atlanta VA Medical Center  Decatur GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth D.","family":"Norrholm","sequence":"additional","affiliation":[{"name":"Mental Health Service Line Atlanta VA Medical Center  Decatur GA USA"},{"name":"Psychiatry and Behavioral Sciences Emory University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4144-1155","authenticated-orcid":false,"given":"Ryan M.","family":"Downey","sequence":"additional","affiliation":[{"name":"Renal Division Department of Medicine Emory University School of Medicine  Atlanta GA USA"},{"name":"Research Service Line Atlanta VA Medical Center  Decatur GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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